Cell Membrane and Ion Channels
Cell membranes are composed of a lipid bilayer and a number of proteins, including ion channels. Accordingly, membranes exhibit both capacitive and resistive responses. Capacitive properties remain fairly constants, while resistive responses depend on the number and type of channels that are open.
Every cell shows a difference in potential between the aqueous solutions on the opposite sides of the plasma membrane. This transmembrane potential is sustained by the selective permeability of the membrane to ions as well as by the activity of electrogenic pumps. It follows that cytosolic ion concentration is tightly controlled with respect to the extracellular environment. On the one hand, this sets the conditions to trigger and propagate bioelectric events in specialized cells and, on the other hand, it sustains controlled changes in the cytosolic ionic concentrations, an important and ubiquitous mechanism of intracellular signalling. The measurement of transmembrane potential, traditionally performed via insertion of an electrode in the cell, has been the starting point to investigate the variation in membrane permeability or, equivalently, its conductance. Such equivalence between biological and electric parameters is motivated by the representation of the cell membrane as a dielectric material (lipid bilayer) that is essentially impermeable to most charged molecules, and causes the membrane to act as a capacitor by separating the charges lying along its interior and exterior surfaces. The opening of selective aqueous pores within transmembrane proteins (ion channels) enables specific ions to move in and out the cell, down their electrochemical gradient, thus temporarily or steadily modifying the membrane conductance.
Ion channels are generally classified according to either their ion selectivity (K+, Na+, Ca2, Cl−) or the type of activation mechanism. According to the latter criterion, main gating mechanisms of ion channel opening can be classified as:                binding of molecules (either in the extracellular or intracellular milieu);        changes in transmembrane potential;        mechanical strain of the cell membrane.        
Cellular permeability is determined by both the type and the number of ion channels present and active in the plasma membrane Recent evidence shows that the expression of channels can be determined not only by the control of their biosynthesis but also by local recycling between inner compartments and cell surface, thereby permitting the rapid adaptation of their functional expression in response to specific signals. Moreover, biologically active molecules whose activity is expressed after their incorporation into the membrane bilayer induce the formation of pores with variable levels of ionic selectivity. This is the case of some antibiotics showing an ohmic behaviour (such as nistatin, amphotericin B, gramicidin) or non-ohmic behaviour (such as alameticin).
The control of ion fluxes (and consequently the membrane permeability) is fundamental for cell life as well as for main cellular functions (neurotransmitters/hormones release, excitability control, gene activation etc.); then it is evident that any alteration of the ionic balance can have important consequences on cell physiology. The wide interest in this field is documented by the introduction of the term “channelopathies” to include all the diseases associated with mutations of ion channels subunits. Therefore, there is the need for an easy and fast screening of candidate compounds able to modulate membrane permeability/conductance by specifically affecting ion channel activities and then acting as channelopathies drugs.